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Open Access Publications from the University of California

Scholarly Works (3 results)

  • Article
  • Peer Reviewed
UC San Francisco Previously Published Works (2011)
There have been several attempts to use gene microarrays from peripheral blood mononuclear cells to identify new biological pathways or targets for therapy in Posttraumatic Stress Disorder (PTSD). The few studies conducted to date have yielded an unclear pattern of findings, perhaps reflecting the use of heterogeneous samples of circulating immune cells for analysis. We used gene microarrays on a homogeneous sample of circulating monocytes to test the hypothesis that chronic PTSD would be associated with elevated inflammatory activity and to identify new pathways dysregulated in the disorder. Forty-nine men (24 PTSD+ and 25 age-matched trauma-exposed PTSD− controls) and 18 women (10 PTSD+ and 8 age-matched PTSD− controls) were recruited. Gene expression microarray analysis was performed on CD14+ monocytes, immune cells that initiate and respond to inflammatory signaling. Male subjects with PTSD had an overall pattern of under-expression of genes on monocytes (47 under-expressed versus 4 over-expressed genes). A rigorous correction for multiple comparisons and verification with q-PCR showed that of only 3 genes that were differentially expressed, all were under-expressed. There was no transcriptional evidence of chronic inflammation in male PTSD+ subjects. In contrast, preliminary data from our pilot female PTSD+ subjects showed a relatively balanced pattern of increased and decreased expression of genes and an increase in activity of pathways related to immune activation. The results indicate differential patterns of monocyte gene expression in PTSD, and the preliminary data from our female pilot subjects are suggestive of gender dimorphism in biologic pathways activated in PTSD. Changes in immune cell gene expression may contribute to medical morbidity in PTSD.
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2011)
    Post-traumatic stress disorder (PTSD) confers an increased risk for disorders with an inflammatory etiology. PTSD-related dysregulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary adrenal (HPA) axis and associatedalterations in inflammatory activity may contribute to thisincreased risk. However, little is known about convergent SNS, HPAand inflammatory signaling at the level of the immune cell transcriptome in PTSD. To explore such signaling, we examined theprevalence of specific transcription factor binding motifsin the promoter regions of differentially expressed genes in monocytesfrom individuals with PTSD and matched controls. Participants included 49 men (24 PTSD+ and 25 trauma-exposed controls)and 18 women (10 PTSD+ and 8 controls). Men with PTSD showed up-regulation of target genes for the NF-κB/Rel familyof transcription factors, which convey inflammatory signals, up-regulation of target genes for CREB/ATF transcription factors,which convey adrenergic signals from the SNS, and down-regulation of target genes for the glucocorticoid receptor, which conveysglucocorticoid signals from the HPA axis. Women with PTSD also showed significant up-regulation of target genes for NF-κBand non-significant down-regulation of target genes for GR,but significant down-regulation of target genes for CREB/ATF.Altered transcriptional control of monocyte gene expression could contribute to exaggerated inflammatory activity in PTSD.
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2011)

      BACKGROUND

      Posttraumatic stress disorder (PTSD) is associated with increased risk for age-related diseases and early mortality. An accelerated rate of biological aging could contribute to this increased risk. To investigate, we assessed leukocyte telomere length (LTL), an emerging marker of biological age, in men and women with and without PTSD. We also examined childhood trauma, a risk factor for both PTSD and short LTL, as a potential contributor to short LTL in PTSD.

       METHODS

      Participants included 43 adults with chronic PTSD (n = 18 with multiple categories of childhood trauma) and 47 control subjects (none with multiple categories of childhood trauma) (mean age = 30.55, SD = 7.44). Exclusion criteria included physical illness, medication use, obesity, alcohol or substance abuse, and pregnancy. Structured clinical interviews were conducted to assess PTSD and other psychiatric disorders and childhood trauma exposure. LTL was measured with a quantitative polymerase chain reaction method.

       RESULTS

      As predicted, participants with PTSD had shorter age-adjusted LTL than control subjects. Exposure to childhood trauma was also associated with short LTL. In fact, childhood trauma seemed to account for the PTSD group difference in LTL; only participants with PTSD and exposure to multiple categories of childhood trauma had significantly shorter LTL than control subjects.

       CONCLUSIONS

      Childhood trauma is associated with short LTL in individuals with PTSD. Chronic exposure to the psychobiological sequelae of childhood trauma could increase risk for PTSD and short LTL. Thus, the lasting psychological impact of exposure to trauma in childhood might be accompanied by equally enduring changes at the molecular level.

       

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